title: A systematic review of sorafenib in Child-Pugh A patients with unresectable hepatocellular carcinoma.
abstract: OBJECTIVE
  Several studies have demonstrated that sorafenib is effective in the treatment of unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the efficacy and safety of sorafenib in Child-Pugh A patients with unresectable HCC. The value of sorafenib treatment in different subgroups was examined.
  
  
  METHODS
  A search of the literature published up to July 2012 was conducted. Pubmed, Embase, and the Cochrane library were searched and only randomized controlled trials were included.
  
  
  RESULTS
  Five randomized controlled trials consisting of 1462 patients with unresectable HCC were included. Meta-analyses demonstrated that sorafenib improved the control rate of the disease [relative risk, 1.85; 95% confidence interval (CI), 1.55, 2.20; P<0.001], decreased the risk for tumor progression (hazard ratios, 0.61; 95% CI, 0.51, 0.73; P<0.001), and decreased mortality (hazard ratios, 0.71; 95% CI, 0.56, 0.89; P<0.001), relative to placebo. Subgroup analyses indicated that sorafenib-based treatments were effective in unresectable HCC regardless of the etiology, performance status, Barcelona Clinic Liver Cancer-stage, alanine transaminase/asparate transaminase, bilirubin, and α-feto protein level, except in the subgroup of prior local therapy. Sorafenib was associated with a higher risk of adverse effects than placebo. The risk for grade 3-4 hand-foot skin reactions, rash or desquamation, diarrhea, and hypertension was much higher in the sorafenib treatment group. These side effects could often be mitigated with appropriate treatment.
  
  
  CONCLUSIONS
  Sorafenib was a moderately effective and safe oral drug for use in Child-Pugh A patients with unresectable HCC. Sorafenib monotherapy is not recommended for treating intermediate-stage HCC. More research is needed on the efficacy of sorafenib treatment in patients with prior local therapy.
authors.affiliation: Departments of *Hepatobiliary Surgery †Pharmacy, The First Affiliated Hospital of Chongqing Medical University ‡Department of Hepatobiliary Surgery, Peoples' Hospital of Changshou District, Chongqing, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Shen
authors.forename: Chengyong
authors.initials: C
authors.lastname: Tang
authors.forename: Yefei
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiong
authors.initials: X
authors.lastname: Yan
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Xufu
authors.initials: X
authors.lastname: Wei
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib